Abstract
Introduction
Difficulties initiating and uptitrating β-blockers due to tolerability can complicate management of heart failure. Among other actions, β-blockers reduce heart rate, which is an important cardiovascular risk factor in heart failure. A new therapeutic strategy is ivabradine, which reduces resting heart rate and is associated with improved outcomes.
Methods
A 5-month, prospective, open-label, nonrandomized single-center study was performed in 69 patients. All patients had chronic heart failure with left ventricular systolic dysfunction in sinus rhythm, each were initiated on 3.125 mg twice daily (bid) carvedilol alone (n = 36) or 3.125 mg bid carvedilol/5 mg bid ivabradine (n = 33), on top of background therapy including angiotensin-converting enzyme inhibitor (88%), diuretics (86%), antiplatelet agents (91%), and statins (90%). Dosages were uptitrated every 2 weeks to 25 mg bid carvedilol in both groups and 7.5 mg bid ivabradine maximum in the carvedilol/ivabradine group. Uptitration of carvedilol lasted 1.9 ± 0.4 months with carvedilol/ivabradine and 2.8 ± 0.6 months with carvedilol alone (P < 0.05).
Results
The patients receiving ivabradine had lower resting heart rate at 5 months (61.6 ± 3.1 versus 70.2 ± 4.4 bpm, P < 0.05). Adding ivabradine to carvedilol in patients with heart failure was associated with increases in the 6-min walk test and ejection fraction (all P < 0.05). Treatment tolerability was satisfactory. Patients receiving ivabradine and carvedilol had lower heart rates and better exercise capacity than those on carvedilol alone.
Conclusion
Adding ivabradine to carvedilol in patients with chronic heart failure improves the uptitration of β-blocker. The results merit further verification in a prospective double-blind study.
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Acknowledgments
Article processing charges for this paper were funded by Servier International, Suresnes, France. No funding was received for the study, which was independently conducted. All named authors meet the ICMJE criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.
Conflict of interest
Andrey Bagriy has given lectures for Servier, Pfizer, Astra Zeneca, Takeda, and Sanofi. E. V. Schukina, O. V. Samoilova, O. A. Pricolota, S. I. Malovichko, A. V. Pricolota, E. A. Bagriy declare no conflicts of interest.
Compliance with ethics guidelines
All procedures followed were in accordance with the ethical standards of the responsible committee (institution and nation) and with the Helsinki Declaration of 1975, as revised in 2006 and 2008. Informed consent was obtained from all patients for being included in the study.
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Bagriy, A.E., Schukina, E.V., Samoilova, O.V. et al. Addition of Ivabradine to β-Blocker Improves Exercise Capacity in Systolic Heart Failure Patients in a Prospective, Open-Label Study. Adv Ther 32, 108–119 (2015). https://doi.org/10.1007/s12325-015-0185-5
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DOI: https://doi.org/10.1007/s12325-015-0185-5